The major phase of this study if designed to test the hypothesis that a mild decrease in dihydrotestosterone (DHT) throughout life will prevent the development of benign prostatic hyperplasia and prostate cancer. To test the hypothesis, a unique population of heterozygote males with a known single allelic defect in the 5alpha-reductase-2 gene and a consequent mild decrease in DHT production will be studied and compared to normal age-matched males from the same community. Unlike homozygous males with 5alpha-reductase-2 deficiency who are pseudohermaphrodites; the heterozygous males are phenotypically normal, have a normally differentiated prostate, but an intermediate biochemical defect in 5alpha-reduction between homozygotes and normals. The genetic status of the males will be determined by DNA SSCP analysis of exon 5 of the 5alpha-reductase gene. A single base change (cytosine --- thymidine) present on exon 5 in heterozygous form in carrier males, and homozygotes form in affected male pseudohermaphrodites, and be detected by SSCP. The field work will be carried out in two Dominican villages where there is extensive inbreeding, and where the largest kindred in the world exists with inherited 5alpha-reductase deficiency, and where the characteristics of homozygote male pseudohermaphrodites with 5alpha- reductase deficiency have been extensively studies by the same principal investigator over many years. The homozygotes have a rudimentary prostate; benign prostatic hyperplasia and prostate cancer have never been reported. At least 400 heterozygous men over age 50 will be studied, and 800 control males. Comparison of prostate parameters will include rectal exam and a urology questionnaire for symptoms of prostatism, serum prostate specific antigen (PSA), and uroflow measurements. Half of each group will undergo random transrectal sonography. In the others it will be performed if serum PSA is greater than 4 ug/1, rectal exam is abnormal, AUA symptom score is greater than 7, or uroflow is less than 15 cc/sec. Prostate biopsy will be performed, if indicated. Urinary 5Beta/5alpha metabolite ratios and serum androgen levels with emphasis on 5alpha-steroids will also be compared. Other physiologic characteristics which appear to be DHT-mediated from previous studies of homozygous male pseudohermaphrodites will also be compared, such as cephalic hair loss, secondary sexual hair distribution and acne. The effect of DHT deficiency on lipid profile and longevity will also be studied. Studies will also continue on male pseudohermaphrodites who are homozygous for the 5-alpha-reductase-2 gene, as it pertains to prostate size, PSA determination and secondary sexual hair distribution.